1. Field of Invention
The present invention relates to synthesis of (S)-2-amino-5-methoxytetralin hydrochloride, and more particularly to a synthetic method and a composition of (S)-2-amino-5-methoxytetralin hydrochloride.
2. Description of Related Arts
Parkinson disease (PD) is also known as paralysis agitans which is a slowly progressive movement disorder and is a type of extrapyramidal conditions. Parkinson's disease is a neurodegenerative disease which is common for the middle-aged and the old and the onset age is usually over 60. The symptoms of Parkinson's disease includes tremor or shaking, rigidity or stiff muscles, slow or limited movement, weakness of face muscle and etc. Patients usually cannot handwriting, have difficulty with walking and balance and are easy to fall. In severe cases, patient cannot take care himself or herself and has to lie in bed. As the number of the world's aging population is increased, the number of people suffering from Parkinson's disease is also increased. Parkinson's disease not only imposes a health hazard to the old, but also seriously affects the normal life of the family members of patients.
The pathogenesis of Parkinson's disease is linked to lack of dopamine, which is a central neurotransmitter. Rotigotine is a dopamine receptor agonists and is tested and proved to its ability to significantly improve the condition of a patient and is an effective medication for treatment of Parkinson's disease.
Rotigotine is developed by Schwarz Biosciences for treatment of early-staged secondary Parkinson's disease and late-staged Parkinson's disease, and has a chemical name of (6S)-6-{propyl[2-(2-thienyl)ethyl]amino}-5,6,7,8-tetrahydro-1-naphthalenol. The trade name of Rotigotine is NEUPRO and its structural formula is:

At present, the synthesis of Rotigotine generally utilizes (S)-2-amino-5-methoxyl-1,2,3,4-tetrahydronaphthalene as the raw material, and the synthesis of (S)-2-amino-5-methoxyl-1,2,3,4-tetrahydronaphthalene mainly include benzylamination or methoxylamination. The two synthetic paths are illustrated as follows:

The two methods as shown above utilize 5-methoxy-2-tetraone as the starting material to produce (R)-2-amino-5-methoxytetralin. Then, (S)-Mandelic acid is used to resolve the desire enantiomer to obtain (S)-2-amino-5-methoxytetralin. However, the yield of the final desired product by chiral resolution is very low in which the yield by benzylamination (which refers to reaction with benzylamine) is only 17% and the yield by methoxyamination (which refers to reaction with methoxyamine) is only 23.5%. Therefore the use of these two methods in pharmaceutical industry is greatly limited.